Related resources
Full-text held externally
- DOI: 10.1002/art.38196
- PMID: 24114500
- UKPMCID: 24114500
Search for item elsewhere
University researcher(s)
Academic department(s)
Novel RA susceptibility locus at 22q12 identified in an extended UK genome wide association study.
Orozco, Gisela; Viatte, Sebastien; Bowes, John; Martin, Paul; Wilson, Anthony G; Morgan, Ann W; Steer, Sophia; Wordsworth, Paul; Hocking, Lynne J; UKRAG_consortium; WTCCC_consortium; BRAGGSS_consortium; Barton, Anne; Worthington, Jane; Eyre, Steve
Arthritis and rheumatism. 2014;66(1):24-30.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- DOI: 10.1002/art.38196
- PMID: 24114500
- UKPMCID: 24114500
Abstract
Objective: The number of confirmed rheumatoid arthritis (RA) loci currently stands at 32, but many lines of evidence indicate that expansion of existing genome wide association studies (GWAS) enhances the power to detect additional loci. The objective of this study was to extend our previous UK RA GWAS adding more independent cases and control samples, with the aim of detecting novel association signals for susceptibility to RA in a homogeneous UK cohort. Methods: We had available 3,223 UK RA cases and 5,272 UK controls, which adds 1,361 cases and 2,334 controls to the original GWAS. The genotype data for all cases was imputed using IMPUTE2. After a stringent QC was applied, 3,034 cases, 5,271 controls and 1,831,729 SNPs were available for analysis. Association testing was performed using PLINK. Results: We found suggestive association to 6 novel RA loci (P<10(-4) ) that have previously been associated with other autoimmune diseases and these SNPs were genotyped in independent samples. We validated association with two loci, one of which was associated at genome wide levels of significance in the combined analysis, identifying a novel RA locus at 22q12 (P = 6.9 x 10(-9) ). In addition, we confirmed association to most of the previously known RA susceptibility loci and found increased evidence of association for 16 loci. Conclusions: A new RA locus mapping to 22q12 has been identified. This study supports the evidence that increasing the power of GWAS enhances novel gene discovery. © 2013 American College of Rheumatology.
Keyword(s)
Rheumatoid arthritis; common variants; genetics; genome wide association study; risk loci